title: Antiobesity pharmacotherapy: new drugs and emerging targets.
abstract: Obesity is a growing pandemic, and related health and economic costs are staggering. Pharmacotherapy, partnered with lifestyle modifications, forms the core of current strategies to reduce the burden of this disease and its sequelae. However, therapies targeting weight loss have a significant history of safety risks, including cardiovascular and psychiatric events. Here, evolving strategies for developing antiobesity therapies, including targets, mechanisms, and developmental status, are highlighted. Progress in this field is underscored by Belviq (lorcaserin) and Qsymia (phentermine/topiramate), the first agents in more than 10 years to achieve regulatory approval for chronic weight management in obese patients. On the horizon, novel insights into metabolism and energy homeostasis reveal guanosine 3',5'-cyclic monophosphate (cGMP) signaling circuits as emerging targets for antiobesity pharmacotherapy. These innovations in molecular discovery may elegantly align with practical off-the-shelf approaches, leveraging existing approved drugs that modulate cGMP levels for the management of obesity.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Lin
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Blomain
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Waldman
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001552:Benzazepines / Q000008:administration & dosage / Q000493:pharmacokinetics; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D055808:Drug Discovery / Q000379:methods / Q000639:trends*; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D010645:Phentermine / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D019440:Anti-Obesity Agents; D001552:Benzazepines; D004338:Drug Combinations; C576188:Qsymia; D005632:Fructose; C506658:lorcaserin; D010645:Phentermine